Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species

BACKGROUND: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. METHODS: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. RESULTS: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. CONCLUSION: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC

Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

<p>Abstract</p> <p>Background</p> <p>Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer.</p> <p>Methods</p> <p>Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice.</p> <p>Results</p> <p>Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression.</p> <p>Conclusion</p> <p>Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Enantioseparation of phenothiazines through capillary electrophoresis with solid phase extraction and polymer based stacking

This study developed a sensitive method involving capillary electrophoresis (CE) coupled with ultraviolet absorption for the simultaneous separation of chiral phenothiazine drugs at nanomolar concentration levels. The method consists of hydroxypropyl-γ-cyclodextrin (Hp-γ-CD) as a chiral selector and poly (diallyldimethylammonium chloride) (PDDAC)-based CE. Five pairs of d,l-phenothiazines were baseline separated using a background electrolyte containing 0.9% PDDAC, 5 mM Hp-γ-CD, and 100 mM tris(hydroxymethyl)aminomethane (Tris)-formate (pH 3.0). The five pairs were successfully stacked on the basis of the difference in viscosity between the PDDAC-containing background electrolyte and the sample solution, with almost no loss of resolution. The combination of a solid-phase extraction and PDDAC-mediated CE can efficiently improve the sensitivity of the phenothiazine enantiomers. Under optimal conditions, calibration graphs displayed the linear range between 6 and 1500 nM, with relative standard deviation values lower than 3.5% (n = 5). Detection limit ranged from 2.1 to 6.3 nM for target analytes, and 607- to 1555-fold enhancement was achieved. The practicality of using the proposed method to determine five pairs of d,l-phenothiazines in urine is also validated, in which recoveries between recoveries of all phenothiazines from urine ranged from 89% to 101%. Keywords: Capillary electrophoresis, Chiral separation, On-line concentration, Phenothiazine, Solid phase extractio

An in Vitro Study on the Effect of Combined Treatment with Photodynamic and Chemical Therapies on Candida albicans

Candida albicans is the most commonly encountered human fungal pathogen, and it is traditionally treated with antimicrobial chemical agents. The antimicrobial effect of these agents is largely weakened by drug resistance and biofilm-associated virulence. Enhancement of the antimicrobial activity of existing agents is needed for effective candidiasis treatment. Our aim was to develop a therapy that combined biofilm disruption with existing antimicrobial agents. Photodynamic therapy (PDT) utilizing curcumin and blue light was tested as an independent therapy and in combination with fluconazole treatment. Viability assays and morphology analysis were used to assess the effectiveness of C. albicans treatment. Results showed that fluconazole treatment decreased the viability of planktonic C. albicans, but the decrease was not as pronounced in adherent C. albicans because its biofilm form was markedly more resistant to the antimicrobiotic. PDT effectively eradicated C. albicans biofilms, and when combined with fluconazole, PDT significantly inhibited C. albicans to a greater extent. This study suggests that the addition of PDT to fluconazole to treat C. albicans infection enhances its effectiveness and can potentially be used clinically

Risk factors for fatal candidemia caused by <it>Candida albicans </it>and non-albicans <it>Candida </it>species

Abstract Background Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. Methods A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. Results There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. Conclusion Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC.</p